PMID- 12954875
OWN - NLM
STAT- MEDLINE
DCOM- 20031002
LR  - 20200225
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 23
IP  - 22
DP  - 2003 Sep 3
TI  - Brain-derived neurotrophic factor activation of NFAT (nuclear factor of activated 
      T-cells)-dependent transcription: a role for the transcription factor NFATc4 in 
      neurotrophin-mediated gene expression.
PG  - 8125-34
AB  - A member of the neurotrophin family, brain-derived neurotrophic factor (BDNF) 
      regulates neuronal survival and differentiation during development. Within the 
      adult brain, BDNF is also important in neuronal adaptive processes, such as the 
      activity-dependent plasticity that underlies learning and memory. These long-term 
      changes in synaptic strength are mediated through alterations in gene expression. 
      However, many of the mechanisms by which BDNF is linked to transcriptional and 
      translational regulation remain unknown. Recently, the transcription factor 
      NFATc4 (nuclear factor of activated T-cells isoform 4) was discovered in neurons, 
      where it is believed to play an important role in long-term changes in neuronal 
      function. Interestingly, NFATc4 is particularly sensitive to the second messenger 
      systems activated by BDNF. Thus, we hypothesized that NFAT-dependent 
      transcription may be an important mediator of BDNF-induced plasticity. In 
      cultured rat CA3-CA1 hippocampal neurons, BDNF activated NFAT-dependent 
      transcription via TrkB receptors. Inhibition of calcineurin blocked BDNF-induced 
      nuclear translocation of NFATc4, thus preventing transcription. Further, 
      phospholipase C was a critical signaling intermediate between BDNF activation of 
      TrkB and the initiation of NFAT-dependent transcription. Both inositol 
      1,4,5-triphosphate (IP3)-mediated release of calcium from intracellular stores 
      and activation of protein kinase C were required for BDNF-induced NFAT-dependent 
      transcription. Finally, increased expression of IP3 receptor 1 and BDNF after 
      neuronal exposure to BDNF was linked to NFAT-dependent transcription. These 
      results suggest that NFATc4 plays a crucial role in neurotrophin-mediated 
      synaptic plasticity.
FAU - Groth, Rachel D
AU  - Groth RD
AD  - Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota 
      55455, USA.
FAU - Mermelstein, Paul G
AU  - Mermelstein PG
LA  - eng
GR  - R01 NS041302/NS/NINDS NIH HHS/United States
GR  - T32 DA007234/DA/NIDA NIH HHS/United States
GR  - DA07234/DA/NIDA NIH HHS/United States
GR  - NS41302/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Calcium Channels)
RN  - 0 (Calcium Channels, L-Type)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Inositol 1,4,5-Trisphosphate Receptors)
RN  - 0 (NFATC Transcription Factors)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Nfatc4 protein, rat)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 3.1.4.- (Type C Phospholipases)
SB  - IM
MH  - Active Transport, Cell Nucleus/drug effects
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/biosynthesis/pharmacology/*physiology
MH  - Calcium Channel Blockers/pharmacology
MH  - Calcium Channels/metabolism
MH  - Calcium Channels, L-Type/drug effects/metabolism
MH  - Cells, Cultured
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - Gene Expression Regulation/drug effects/*physiology
MH  - Inositol 1,4,5-Trisphosphate Receptors
MH  - NFATC Transcription Factors
MH  - Nerve Growth Factors/*physiology
MH  - Nerve Tissue Proteins/*metabolism
MH  - Pyramidal Cells/cytology/drug effects/metabolism
MH  - Rats
MH  - Receptor, trkB/metabolism
MH  - Receptors, Cytoplasmic and Nuclear/metabolism
MH  - Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/metabolism
MH  - Signal Transduction/drug effects/physiology
MH  - Transcription Factors/*metabolism
MH  - Transcription, Genetic/*drug effects
MH  - Type C Phospholipases/metabolism
PMC - PMC6740488
EDAT- 2003/09/05 05:00
MHDA- 2003/10/03 05:00
PMCR- 2004/03/03
CRDT- 2003/09/05 05:00
PHST- 2003/09/05 05:00 [pubmed]
PHST- 2003/10/03 05:00 [medline]
PHST- 2003/09/05 05:00 [entrez]
PHST- 2004/03/03 00:00 [pmc-release]
AID - 23/22/8125 [pii]
AID - 10.1523/JNEUROSCI.23-22-08125.2003 [doi]
PST - ppublish
SO  - J Neurosci. 2003 Sep 3;23(22):8125-34. doi: 10.1523/JNEUROSCI.23-22-08125.2003.